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PeptideAI
In vitro onlyskintanning

Melitane

The mirror image of Melanostatine: an alpha-MSH mimic that switches MC1R on to deepen pigment and improve the skin's own UV defence, without an injection.

Also known as Acetyl Hexapeptide-1, Ac-Nle-Ala-His-D-Phe-Arg-Trp-NH2, MC1R agonist peptide, Melitane

In vitro only — Cell or tissue studies. A mechanism, not yet an effect in a living body.

The MC1R agonist pharmacology of the Nle/D-Phe alpha-MSH core is extremely well established. Melitane's specific skin-colour and photoprotection claims come from supplier explant and panel work, not independent trials.

How it works

Every melanocortin peptide, from alpha-MSH to Melanotan II to setmelanotide, is built around the His-Phe-Arg-Trp message sequence. Acetyl hexapeptide-1 presents that core with a norleucine substitution for the oxidation-prone methionine and a D-phenylalanine for protease resistance — the same two modifications that produced NDP-MSH. At MC1R it raises cAMP, induces MITF and tyrosinase, increases melanin content and extends melanocyte dendrites so pigment transfers to more keratinocytes. Supplier work also reports reduced UV-induced DNA damage and reduced inflammatory cytokine release, which is consistent with the known photoprotective role of eumelanin. Unlike injected Melanotan II it is confined to the applied area and has no systemic melanocortin activity, so no nausea, no flushing and no libido effects.

Targets: Melanocortin-1 receptor (MC1R), Tyrosinase and MITF, Melanocyte dendricity, UV-induced DNA damage

Dosing

ProtocolDoseFrequencyRoute
Self-tan or photoprotection serumApplied evenly to the whole treated area, or you will get patchy colour.—once or twice dailytopical
  • · Trade solution used at 2-5% of the formula. From raw powder, 0.001-0.01% w/w. Even application matters more than concentration here.

Cycling

Continuous use to maintain colour; pigment fades over normal epidermal turnover of roughly 4-6 weeks after stopping.

Work out your exact syringe units →

Pharmacology

Half-life
Not established topically.
Onset
Colour changes build over 4-8 weeks of daily use — far slower and subtler than injected melanocortins.
Routes
topical
Molecule
Synthetic acetylated hexapeptide amide (alpha-MSH core analogue)
Sequence length
6 amino acids
Molecular weight
870 Da

Handling

Diluent
Distilled or deionised water
Typical mix
20 or 50 mL
Vial sizes
50, 100, 200 mg
Lyophilised
Sealed, cool and dry; freezer for long-term.
Reconstituted
Refrigerated and preserved.

Mixing

Water soluble.

Side effects

  • commonUneven or patchy pigmentation— Almost always an application-technique problem.
  • commonDarkening of existing freckles, moles and sun spots— Existing pigmented lesions respond too, which can make surveillance harder.

Do not use if

  • Melasma or post-inflammatory hyperpigmentation — you are pushing exactly the wrong direction.
  • A history of melanoma or dysplastic naevi — deliberately stimulating melanocytes in someone under pigmented-lesion surveillance is a bad trade.

Combining it

  • conflictmelanostatine-5 — Opposing agonist and antagonist at the same receptor.
  • redundantmelanotan-i — Same MC1R target; the injectable does it systemically and far more strongly.
  • conflictdecapeptide-12 — Tyrosinase inhibition works directly against the intended effect.

What to monitor

  • · Photograph moles and pigmented lesions before starting so you have a baseline for comparison.

Legal status

Cosmetic ingredient (INCI Acetyl Hexapeptide-1) approved worldwide. Unlike injectable melanotans, this has no regulatory problem.

References

  • Lucas Meyer Cosmetics Melitane technical dossier (other)
  • Sawyer et al. 1980, 4-norleucine-7-D-phenylalanine-alpha-MSH, a highly potent alpha-melanotropin (preclinical)

Mechanism in depth

The core structural fact is that every melanocortin ligand ever made — alpha-MSH itself, NDP-MSH, Melanotan II, afamelanotide, setmelanotide, bremelanotide — is built around the same four-residue message sequence His-Phe-Arg-Trp. Sawyer and Hruby showed in 1980 that substituting norleucine for Met4 and D-phenylalanine for Phe7 in alpha-MSH produced a molecule with dramatically increased potency and duration, and that compound, NDP-MSH, is the parent of essentially the entire modern melanocortin field. Acetyl hexapeptide-1 presents that stabilised core. At MC1R it is a Gs-coupled agonist: cAMP rises, PKA activates, CREB is phosphorylated, MITF is transcribed, and MITF drives tyrosinase, TYRP1 and DCT along with melanosome biogenesis and dendrite extension. The result is more eumelanin, distributed to more keratinocytes. The photoprotection argument is real and has human evidence behind it in the injected form — Barnetson's group showed that NDP-MSH significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers, which is the strongest evidence any melanocortin has for the DNA-protection claim. Note carefully that this was injected NDP-MSH, not a topical hexapeptide. The other MC1R effect that gets less attention is anti-inflammatory: MC1R signalling suppresses NF-kB activation, which is why melanocortins reduce cytokine release independently of pigment. The supplier's claims about reduced UV-induced DNA damage and reduced inflammatory cytokines are consistent with that established biology even though the specific data are theirs.

What usually goes wrong

Patchy colour, and it is almost always application technique. Melanocyte density and MC1R responsiveness vary across the face, so uneven application produces uneven pigment and the result looks like a bad self-tan. Apply evenly to the whole treated area, every time. The more serious issue is pigmented lesion surveillance. Existing naevi, freckles and lentigines contain melanocytes and they respond to MC1R agonism too, so they darken. If you have a lot of moles, a family history of melanoma, or you are under dermatological surveillance, deliberately stimulating melanocytes and making your baseline photographs useless is a genuinely bad trade. Photograph everything before starting. And the obvious one: using it on melasma or post-inflammatory hyperpigmentation is pushing hard in the wrong direction.

Pharmacokinetics

Crosses blood-brain barrier
no
Metabolism
The norleucine substitution removes the oxidation-prone methionine and the D-phenylalanine blocks the principal proteolytic cleavage site. These are exactly the two modifications Sawyer's group introduced in 1980 to create NDP-MSH, and they are the reason that molecule had, in the original title's phrasing, ultralong biological activity.
Elimination
No meaningful systemic exposure from topical application, which is the entire safety advantage over injected melanocortins — no nausea, no flushing, no priapism, no systemic melanocortin receptor engagement.

Receptor targets

  • Melanocortin-1 receptor (MC1R) — The NDP-MSH parent is subnanomolar at MC1R; no affinity published for the cosmetic hexapeptide specifically

    Gs-coupled agonism — cAMP up, PKA activation, CREB phosphorylation, MITF induction.

  • MITF / tyrosinase / TYRP1 / DCT (downstream) — Transcriptional

    Increased eumelanin synthesis and melanosome production.

  • Melanocyte dendricity — Downstream of cAMP

    Longer dendrites mean pigment is transferred to more surrounding keratinocytes, which is what turns melanin synthesis into visible colour.

  • NF-kB signalling — Established MC1R effect, not specific to this ligand

    Reduced inflammatory cytokine release — the basis for the photoprotection-beyond-pigment claims.

Trials

  • Ye et al. evaluation of a supramolecular retinol plus acetyl hexapeptide-1 essence in middle-aged Chinese women (Skin Health and Disease) Clinical evaluation · 2023

    Improvement of mild photoaged facial skin. Multi-ingredient with retinol, so it cannot isolate the hexapeptide, but it is indexed human data on a formulation containing it.

  • Sakhiya et al. case report of premature hair greying treated with Melitane 5% plus oral supplements (Indian Journal of Pharmacology) Single case report · n=1 · 2019

    Repigmentation of prematurely grey hair. A single case with concurrent oral supplements — interesting as a signal for the follicular melanocyte application, worthless as evidence.

What to expect, and when

Week 4-8: colour builds gradually. This is far slower and subtler than injected melanocortins, where visible tanning appears within days. Discontinuation: colour fades over normal epidermal turnover of roughly four to six weeks.

Stacking and comparisons

This is the compound where conflicts matter most, because half of the popular skincare ingredient list works directly against it. Any tyrosinase inhibitor — decapeptide-12, kojic acid, arbutin, azelaic acid, hydroquinone, vitamin C at brightening concentrations — cancels the intended effect. Melanostatine-5 is the exact pharmacological opposite. Niacinamide inhibits melanosome transfer to keratinocytes, which is precisely the last step Melitane is trying to enhance, so it belongs on the conflict list too even though nobody thinks of it that way. What pairs sensibly is nothing much; this is a single-purpose ingredient. Against injected melanotans the comparison is stark: Melitane is confined to the treated area with no systemic melanocortin activity, so no nausea, no flushing, no libido effects and no darkening of untreated moles elsewhere on the body.

Against injected Melanotan I or II, Melitane is vastly weaker, vastly slower, confined to the treated area, and free of the systemic melanocortin side effect profile that makes injected melanotans a genuinely risky proposition. It is also legal as a cosmetic ingredient everywhere, which injected melanotans are not. Against DHA self-tanner, DHA colours the stratum corneum by Maillard reaction and gives no photoprotection at all; Melitane produces real eumelanin, which does. Against Melanostatine-5, direct opposites at the same receptor.

Rough cost

$20–$90/month. Raw acetyl hexapeptide-1 runs roughly $60-150 per gram at 0.001-0.01% use levels. Finished products $25-90 a month. Market observation, not a sourced pricing study.

Genuinely uncertain

  • No independent trial of topical acetyl hexapeptide-1 on human skin colour exists. The photoprotection data come from injected NDP-MSH, a different molecule delivered a different way.
  • No binding affinity has been published for the cosmetic hexapeptide at MC1R.
  • Whether an 870 Da peptide reaches basal melanocytes in useful quantity has never been measured.
  • The molecular weight of 870.0 Da in the Core record is plausible for the acetylated amidated hexapeptide but is unconfirmed against a primary source.
  • Whether topically induced pigment confers the same UV protection as endogenous or injected-melanocortin-induced pigment is untested.
  • The follicular repigmentation application is supported by one case report with confounding oral supplements.

Papers